Method and system for microbiome-derived diagnostics and therapeutics

ABSTRACT

A method for diagnosing and treating an immune microbial dysfunction in a subject, the method comprising: receiving an aggregate set of biological samples from a population of subjects; generating at least one of a microbiome composition dataset and a microbiome functional diversity dataset for the population of subjects; generating a characterization of the immune microbial dysfunction based upon features extracted from at least one of the microbiome composition dataset and the microbiome functional diversity dataset, wherein the characterization is diagnostic of at least one of Crohn&#39;s disease, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), ulcerative colitis, and celiac disease; based upon the characterization, generating a therapy model configured to correct the immune microbial dysfunction; and at an output device associated with the subject, promoting a therapy to the subject based upon the characterization and the therapy model.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/919,614, filed 21 Oct. 2017, which claims the benefit of U.S.Provisional Application Ser. No. 62/066,369 filed 21 Oct. 2014, U.S.Provisional Application Ser. No. 62/087,551 filed 4 Dec. 2014, U.S.Provisional Application Ser. No. 62/092,999 filed 17 Dec. 2014, U.S.Provisional Application Ser. No. 62/147,376 filed 14 Apr. 2015, U.S.Provisional Application Ser. No. 62/147,212 filed 14 Apr. 2015, U.S.Provisional Application Ser. No. 62/147,362 filed 14 Apr. 2015, U.S.Provisional Application Ser. No. 62/146,855 filed 13 Apr. 2015, and U.S.Provisional Application Ser. No. 62/206,654 filed 18 Aug. 2015, whichare each incorporated in its entirety herein by this reference.

TECHNICAL FIELD

This invention relates generally to the field of microbiology and morespecifically to a new and useful method and system formicrobiome-derived diagnostics and therapeutics in the field ofmicrobiology.

BACKGROUND

A microbiome is an ecological community of commensal, symbiotic, andpathogenic microorganisms that are associated with an organism. Thehuman microbiome comprises over 10 times more microbial cells than humancells, but characterization of the human microbiome is still in nascentstages due to limitations in sample processing techniques, geneticanalysis techniques, and resources for processing large amounts of data.Nonetheless, the microbiome is suspected to play at least a partial rolein a number of health/disease-related states (e.g., preparation forchildbirth, diabetes, auto-immune disorders, gastrointestinal disorders,rheumatoid disorders, neurological disorders, etc.). Given the profoundimplications of the microbiome in affecting a subject's health, effortsrelated to the characterization of the microbiome, the generation ofinsights from the characterization, and the generation of therapeuticsconfigured to rectify states of dysbiosis should be pursued. Currentmethods and systems for analyzing the microbiomes of humans andproviding therapeutic measures based on gained insights have, however,left many questions unanswered. In particular, methods forcharacterizing certain health conditions and therapies (e.g., probiotictherapies) tailored to specific subjects have not been viable due tolimitations in current technologies.

As such, there is a need in the field of microbiology for a new anduseful method and system for characterizing health conditions in anindividualized and population-wide manner. This invention creates such anew and useful method and system.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A is a flowchart of an embodiment of a first method for generatingmicrobiome-derived diagnostics and therapeutics;

FIG. 1B is a flowchart of an embodiment of a second method forgenerating microbiome-derived diagnostics and therapeutics;

FIG. 2 depicts an embodiment of a method and system for generatingmicrobiome-derived diagnostics and therapeutics;

FIG. 3 depicts variations of a portion of an embodiment of a method forgenerating microbiome-derived diagnostics and therapeutics;

FIG. 4 depicts a variation of a process for generation of a model in anembodiment of a method and system for generating microbiome-deriveddiagnostics and therapeutics;

FIG. 5 depicts variations of mechanisms by which probiotic-basedtherapies operate in an embodiment of a method for characterizing ahealth condition; and

FIG. 6 depicts examples of therapy-related notification provision in anexample of a method for generating microbiome-derived diagnostics andtherapeutics.

DESCRIPTION OF THE EMBODIMENTS

The following description of the embodiments of the invention is notintended to limit the invention to these embodiments, but rather toenable any person skilled in the art to make and use this invention.

1. First Method

As shown in FIG. 1A, a first method 100 for diagnosing and treating animmune microbial dysfunction comprises: receiving an aggregate set ofbiological samples from a population of subjects S110; characterizing amicrobiome composition and/or functional features for each of theaggregate set of biological samples associated with the population ofsubjects, thereby generating at least one of a microbiome compositiondataset and a microbiome functional diversity dataset for the populationof subjects S120; receiving a supplementary dataset, associated with atleast a subset of the population of subjects, wherein the supplementarydataset is informative of characteristics associated with the immunemicrobial dysfunction S130; and generating a characterization of theimmune microbial dysfunction based upon the supplementary dataset andfeatures extracted from at least one of the microbiome compositiondataset and the microbiome functional diversity dataset S140. In somevariations, the first method 100 can further include: based upon thecharacterization, generating a therapy model configured to correct theimmune microbial dysfunction S150.

The first method 100 functions to generate models that can be used tocharacterize and/or diagnose subjects according to at least one of theirmicrobiome composition and functional features (e.g., as a clinicaldiagnostic, as a companion diagnostic, etc.), and provide therapeuticmeasures (e.g., probiotic-based therapeutic measures, phage-basedtherapeutic measures, small-molecule-based therapeutic measures,clinical measures, etc.) to subjects based upon microbiome analysis fora population of subjects. As such, data from the population of subjectscan be used to characterize subjects according to their microbiomecomposition and/or functional features, indicate states of health andareas of improvement based upon the characterization(s), and promote oneor more therapies that can modulate the composition of a subject'smicrobiome toward one or more of a set of desired equilibrium states.Variations of the method 100 can further facilitate monitoring and/oradjusting of therapies provided to a subject, for instance, throughreception, processing, and analysis of additional samples from a subjectthroughout the course of therapy. In specific examples, the method 100can be used to promote targeted therapies to subjects suffering from animmune microbial dysfunction. In specific examples, the method 100 canbe used for characterization of and/or therapeutic intervention for oneor more of: Crohn's disease, inflammatory bowel disease (IBD), irritablebowel syndrome (IBS), ulcerative colitis, and celiac disease.

As such, in some embodiments, outputs of the first method 100 can beused to generate diagnostics and/or provide therapeutic measures for asubject based upon an analysis of the subject's microbiome compositionand/or functional features of the subject's microbiome. Thus, as shownin FIG. 1B, a second method 200 derived from at least one output of thefirst method 100 can include: receiving a biological sample from asubject S210; characterizing the subject with a form of an immunemicrobial dysfunction based upon processing a microbiome dataset derivedfrom the biological sample S220; and promoting a therapy to the subjectwith the immune microbial dysfunction based upon the characterizationand the therapy model S230. Embodiments, variations, and examples of thesecond method 200 are described in more detail below.

The methods 100, 200 function to generate models that can be used toclassify individuals and/or provide therapeutic measures (e.g., therapyrecommendations, therapies, therapy regimens, etc.) to individuals basedupon microbiome analysis for a population of individuals. As such, datafrom the population of individuals can be used to generate models thatcan classify individuals according to their microbiome compositions(e.g., as a diagnostic measure), indicate states of health and areas ofimprovement based upon the classification(s), and/or provide therapeuticmeasures that can push the composition of an individual's microbiometoward one or more of a set of improved equilibrium states. Variationsof the second method 200 can further facilitate monitoring and/oradjusting of therapies provided to an individual, for instance, throughreception, processing, and analysis of additional samples from anindividual throughout the course of therapy.

In one application, at least one of the methods 100, 200 is implemented,at least in part, at a system 300, as shown in FIG. 2, that receives abiological sample derived from the subject (or an environment associatedwith the subject) by way of a sample reception kit, and processes thebiological sample at a processing system implementing a characterizationprocess and a therapy model configured to positively influence amicroorganism distribution in the subject (e.g., human, non-humananimal, environmental ecosystem, etc.). In variations of theapplication, the processing system can be configured to generate and/orimprove the characterization process and the therapy model based uponsample data received from a population of subjects. The method 100 can,however, alternatively be implemented using any other suitable system(s)configured to receive and process microbiome-related data of subjects,in aggregation with other information, in order to generate models formicrobiome-derived diagnostics and associated therapeutics. Thus, themethod 100 can be implemented for a population of subjects (e.g.,including the subject, excluding the subject), wherein the population ofsubjects can include patients dissimilar to and/or similar to thesubject (e.g., in health condition, in dietary needs, in demographicfeatures, etc.). Thus, information derived from the population ofsubjects can be used to provide additional insight into connectionsbetween behaviors of a subject and effects on the subject's microbiome,due to aggregation of data from a population of subjects.

Thus, the methods 100, 200 can be implemented for a population ofsubjects (e.g., including the subject, excluding the subject), whereinthe population of subjects can include subjects dissimilar to and/orsimilar to the subject (e.g., health condition, in dietary needs, indemographic features, etc.). Thus, information derived from thepopulation of subjects can be used to provide additional insight intoconnections between behaviors of a subject and effects on the subject'smicrobiome, due to aggregation of data from a population of subjects.

1.1 First Method: Sample Handling

Block S110 recites: receiving an aggregate set of biological samplesfrom a population of subjects, which functions to enable generation ofdata from which models for characterizing subjects and/or providingtherapeutic measures to subjects can be generated. In Block S110,biological samples are preferably received from subjects of thepopulation of subjects in a non-invasive manner. In variations,non-invasive manners of sample reception can use any one or more of: apermeable substrate (e.g., a swab configured to wipe a region of asubject's body, toilet paper, a sponge, etc.), a non-permeable substrate(e.g., a slide, tape, etc.), a container (e.g., vial, tube, bag, etc.)configured to receive a sample from a region of an subject's body, andany other suitable sample-reception element. In a specific example,samples can be collected from one or more of a subject's nose, skin,genitals, mouth, and gut in a non-invasive manner (e.g., using a swaband a vial). However, one or more biological samples of the set ofbiological samples can additionally or alternatively be received in asemi-invasive manner or an invasive manner. In variations, invasivemanners of sample reception can use any one or more of: a needle, asyringe, a biopsy element, a lance, and any other suitable instrumentfor collection of a sample in a semi-invasive or invasive manner. Inspecific examples, samples can comprise blood samples, plasma/serumsamples (e.g., to enable extraction of cell-free DNA), and tissuesamples.

In the above variations and examples, samples can be taken from thebodies of subjects without facilitation by another entity (e.g., acaretaker associated with an individual, a health care professional, anautomated or semi-automated sample collection apparatus, etc.), or canalternatively be taken from bodies of individuals with the assistance ofanother entity. In one example, wherein samples are taken from thebodies of subjects without facilitation by another entity in the sampleextraction process, a sample-provision kit can be provided to a subject.In the example, the kit can include one or more swabs for sampleacquisition, one or more containers configured to receive the swab(s)for storage, instructions for sample provision and setup of a useraccount, elements configured to associate the sample(s) with the subject(e.g., barcode identifiers, tags, etc.), and a receptacle that allowsthe sample(s) from the individual to be delivered to a sample processingoperation (e.g., by a mail delivery system). In another example, whereinsamples are extracted from the user with the help of another entity, oneor more samples can be collected in a clinical or research setting froma subject (e.g., during a clinical appointment).

In Block S110, the aggregate set of biological samples is preferablyreceived from a wide variety of subjects, and can involve samples fromhuman subjects and/or non-human subjects. In relation to human subjects,Block S110 can include receiving samples from a wide variety of humansubjects, collectively including subjects of one or more of: differentdemographics (e.g., genders, ages, marital statuses, ethnicities,nationalities, socioeconomic statuses, sexual orientations, etc.),different health conditions (e.g., health and disease states), differentliving situations (e.g., living alone, living with pets, living with asignificant other, living with children, etc.), different dietary habits(e.g., omnivorous, vegetarian, vegan, sugar consumption, acidconsumption, etc.), different behavioral tendencies (e.g., levels ofphysical activity, drug use, alcohol use, etc.), different levels ofmobility (e.g., related to distance traveled within a given timeperiod), biomarker states (e.g., cholesterol levels, lipid levels,etc.), weight, height, body mass index, genotypic factors, and any othersuitable trait that has an effect on microbiome composition. As such, asthe number of subjects increases, the predictive power of feature-basedmodels generated in subsequent blocks of the method 100 increases, inrelation to characterizing of a variety of subjects based upon theirmicrobiomes. Additionally or alternatively, the aggregate set ofbiological samples received in Block S110 can include receivingbiological samples from a targeted group of similar subjects in one ormore of: demographic traits, health conditions, living situations,dietary habits, behavior tendencies, levels of mobility, and any othersuitable trait that has an effect on microbiome composition.

In some embodiments, receiving the aggregate set of biological samplesin Block S110 can be performed according to embodiments, variations, andexamples of sample reception as described in U.S. application Ser. No.14/593,424 filed on 9 Jan. 2015 and entitled “Method and System forMicrobiome Analysis”, which is incorporated herein in its entirety bythis reference. However, receiving the aggregate set of biologicalsamples in Block S110 can additionally or alternatively be performed inany other suitable manner. Furthermore, some variations of the firstmethod 100 can omit Block S110, with processing of data derived from aset of biological samples performed as described below in subsequentblocks of the method 100.

1.2 First Method: Sample Analysis, Microbiome Composition, andFunctional Aspects

Block S120 recites: characterizing a microbiome composition and/orfunctional features for each of the aggregate set of biological samplesassociated with a population of subjects, thereby generating at leastone of a microbiome composition dataset and a microbiome functionaldiversity dataset for the population of subjects. Block S120 functionsto process each of the aggregate set of biological samples, in order todetermine compositional and/or functional aspects associated with themicrobiome of each of a population of subjects. Compositional andfunctional aspects can include compositional aspects at themicroorganism level, including parameters related to distribution ofmicroorgansims across different groups of kingdoms, phyla, classes,orders, families, genera, species, subspecies, strains, infraspeciestaxon (e.g., as measured in total abundance of each group, relativeabundance of each group, total number of groups represented, etc.),and/or any other suitable taxa. Compositional and functional aspects canalso be represented in terms of operational taxonomic units (OTUs).Compositional and functional aspects can additionally or alternativelyinclude compositional aspects at the genetic level (e.g., regionsdetermined by multilocus sequence typing, 16S sequences, 18S sequences,ITS sequences, other genetic markers, other phylogenetic markers, etc.).Compositional and functional aspects can include the presence or absenceor the quantity of genes associated with specific functions (e.g.,enzyme activities, transport functions, immune activities, etc.).Outputs of Block S120 can thus be used to provide features of interestfor the characterization process of Block S140, wherein the features canbe microorganism-based (e.g., presence of a genus of bacteria),genetic-based (e.g., based upon representation of specific geneticregions and/or sequences) and/or functional-based (e.g., presence of aspecific catalytic activity, presence of metabolic pathways, etc.).

In one variation, Block S120 can include characterization of featuresbased upon identification of phylogenetic markers derived from bacteriaand/or archaea in relation to gene families associated with one or moreof: ribosomal protein S2, ribosomal protein S3, ribosomal protein S5,ribosomal protein S7, ribosomal protein S8, ribosomal protein S9,ribosomal protein S10, ribosomal protein S11, ribosomal protein S12/S23,ribosomal protein S13, ribosomal protein S15P/S13e, ribosomal proteinS17, ribosomal protein S19, ribosomal protein L1, ribosomal protein L2,ribosomal protein L3, ribosomal protein L4/L1e, ribosomal protein L5,ribosomal protein L6, ribosomal protein L10, ribosomal protein L11,ribosomal protein L13, ribosomal protein L14b/L23e, ribosomal proteinL15, ribosomal protein L16/L10E, ribosomal protein L18P/L5E, ribosomalprotein L22, ribosomal protein L24, ribosomal protein L25/L23, ribosomalprotein L29, translation elongation factor EF-2, translation initiationfactor IF-2, metalloendopeptidase, ffh signal recognition particleprotein, phenylalanyl-tRNA synthetase alpha subunit, phenylalanyl-tRNAsynthetase beta subunit, tRNA pseudouridine synthase B, porphobilinogendeaminase, phosphoribosylformylglycinamidine cyclo-ligase, andribonuclease HII. However, the markers can include any other suitablemarker(s)

Characterizing the microbiome composition and/or functional features foreach of the aggregate set of biological samples in Block S120 thuspreferably includes a combination of sample processing techniques (e.g.,wet laboratory techniques) and computational techniques (e.g., utilizingtools of bioinformatics) to quantitatively and/or qualitativelycharacterize the microbiome and functional features associated with eachbiological sample from a subject or population of subjects.

In variations, sample processing in Block S120 can include any one ormore of: lysing a biological sample, disrupting membranes in cells of abiological sample, separation of undesired elements (e.g., RNA,proteins) from the biological sample, purification of nucleic acids(e.g., DNA) in a biological sample, amplification of nucleic acids fromthe biological sample, further purification of amplified nucleic acidsof the biological sample, and sequencing of amplified nucleic acids ofthe biological sample. Thus, portions of Block S120 can be implementedusing embodiments, variations, and examples of the sample handlingnetwork and/or computing system as described in U.S. application Ser.No. 14/593,424 filed on 9 Jan. 2015 and entitled “Method and System forMicrobiome Analysis”, which is incorporated herein in its entirety bythis reference. Thus the computing system implementing one or moreportions of the method 100 can be implemented in one or more computingsystems, wherein the computing system(s) can be implemented at least inpart in the cloud and/or as a machine (e.g., computing machine, server,mobile computing device, etc.) configured to receive a computer-readablemedium storing computer-readable instructions. However, Block S120 canbe performed using any other suitable system(s).

In variations, lysing a biological sample and/or disrupting membranes incells of a biological sample preferably includes physical methods (e.g.,bead beating, nitrogen decompression, homogenization, sonication), whichomit certain reagents that produce bias in representation of certainbacterial groups upon sequencing. Additionally or alternatively, lysingor disrupting in Block S120 can involve chemical methods (e.g., using adetergent, using a solvent, using a surfactant, etc.). Additionally oralternatively, lysing or disrupting in Block S120 can involve biologicalmethods. In variations, separation of undesired elements can includeremoval of RNA using RNases and/or removal of proteins using proteases.In variations, purification of nucleic acids can include one or more of:precipitation of nucleic acids from the biological samples (e.g., usingalcohol-based precipitation methods), liquid-liquid based purificationtechniques (e.g., phenol-chloroform extraction), chromatography-basedpurification techniques (e.g., column adsorption), purificationtechniques involving use of binding moiety-bound particles (e.g.,magnetic beads, buoyant beads, beads with size distributions,ultrasonically responsive beads, etc.) configured to bind nucleic acidsand configured to release nucleic acids in the presence of an elutionenvironment (e.g., having an elution solution, providing a pH shift,providing a temperature shift, etc.), and any other suitablepurification techniques.

In variations, performing an amplification operation S123 on purifiednucleic acids can include performing one or more of: polymerase chainreaction (PCR)-based techniques (e.g., solid-phase PCR, RT-PCR, qPCR,multiplex PCR, touchdown PCR, nanoPCR, nested PCR, hot start PCR, etc.),helicase-dependent amplification (HDA), loop mediated isothermalamplification (LAMP), self-sustained sequence replication (3SR), nucleicacid sequence based amplification (NASBA), strand displacementamplification (SDA), rolling circle amplification (RCA), ligase chainreaction (LCR), and any other suitable amplification technique. Inamplification of purified nucleic acids, the primers used are preferablyselected to prevent or minimize amplification bias, as well asconfigured to amplify nucleic acid regions/sequences (e.g., of the 16Sregion, the 18S region, the ITS region, etc.) that are informativetaxonomically, phylogenetically, for diagnostics, for formulations(e.g., for probiotic formulations), and/or for any other suitablepurpose. Thus, universal primers (e.g., a F27-R338 primer set for 16SRNA, a F515-R806 primer set for 16S RNA, etc.) configured to avoidamplification bias can be used in amplification. Primers used invariations of Block S110 can additionally or alternatively includeincorporated barcode sequences specific to each biological sample, whichcan facilitate identification of biological samples post-amplification.Primers used in variations of Block S110 can additionally oralternatively include adaptor regions configured to cooperate withsequencing techniques involving complementary adaptors (e.g., accordingto protocols for Illumina Sequencing).

Identification of a primer set for a multiplexed amplification operationcan be performed according to embodiments, variations, and examples ofmethods described in U.S. App. No. 62/206,654 filed 18 Aug. 2015 andentitled “Method and System for Multiplex Primer Design”, which isherein incorporated in its entirety by this reference. Performing amultiplexed amplification operation using a set of primers in Block S123can additionally or alternatively be performed in any other suitablemanner.

Additionally or alternatively, as shown in FIG. 3, Block S120 canimplement any other step configured to facilitate processing (e.g.,using a Nextera kit) for performance of a fragmentation operation S122(e.g., fragmentation and tagging with sequencing adaptors) incooperation with the amplification operation S123 (e.g., S122 can beperformed after S123, S122 can be performed before S123, S122 can beperformed substantially contemporaneously with S123, etc) Furthermore,Blocks S122 and/or S123 can be performed with or without a nucleic acidextraction step. For instance, extraction can be performed prior toamplification of nucleic acids, followed by fragmentation, and thenamplification of fragments. Alternatively, extraction can be performed,followed by fragmentation and then amplification of fragments. As such,in some embodiments, performing an amplification operation in Block S123can be performed according to embodiments, variations, and examples ofamplification as described in U.S. application Ser. No. 14/593,424 filedon 9 Jan. 2015 and entitled “Method and System for Microbiome Analysis”.Furthermore, amplification in Block S123 can additionally oralternatively be performed in any other suitable manner.

In a specific example, amplification and sequencing of nucleic acidsfrom biological samples of the set of biological samples includes:solid-phase PCR involving bridge amplification of DNA fragments of thebiological samples on a substrate with oligo adapters, whereinamplification involves primers having a forward index sequence (e.g.,corresponding to an Illumina forward index for MiSeq/NextSeq/HiSeqplatforms) or a reverse index sequence (e.g., corresponding to anIllumina reverse index for MiSeq/NextSeq/HiSeq platforms), a forwardbarcode sequence or a reverse barcode sequence, a transposase sequence(e.g., corresponding to a transposase binding site forMiSeq/NextSeq/HiSeq platforms), a linker (e.g., a zero, one, or two-basefragment configured to reduce homogeneity and improve sequence results),an additional random base, and a sequence for targeting a specifictarget region (e.g., 16S region, 18S region, ITS region). Amplificationand sequencing can further be performed on any suitable amplicon, asindicated throughout the disclosure. In the specific example, sequencingcomprises Illumina sequencing (e.g., with a HiSeq platform, with a MiSeqplatform, with a NextSeq platform, etc.) using a sequencing-by-synthesistechnique.

Some variations of sample processing in Block S120 can include furtherpurification of amplified nucleic acids (e.g., PCR products) prior tosequencing, which functions to remove excess amplification elements(e.g., primers, dNTPs, enzymes, salts, etc.). In examples, additionalpurification can be facilitated using any one or more of: purificationkits, buffers, alcohols, pH indicators, chaotropic salts, nucleic acidbinding filters, centrifugation, and any other suitable purificationtechnique.

In variations, computational processing in Block S120 can include anyone or more of: performing a sequencing analysis operation S124including identification of microbiome-derived sequences (e.g., asopposed to subject sequences and contaminants), performing an alignmentand/or mapping operation S125 of microbiome-derived sequences (e.g.,alignment of fragmented sequences using one or more of single-endedalignment, ungapped alignment, gapped alignment, pairing), andgenerating features S126 derived from compositional and/or functionalaspects of the microbiome associated with a biological sample.

Performing the sequencing analysis operation S124 with identification ofmicrobiome-derived sequences can include mapping of sequence data fromsample processing to a subject reference genome (e.g., provided by theGenome Reference Consortium), in order to remove subject genome-derivedsequences. Unidentified sequences remaining after mapping of sequencedata to the subject reference genome can then be further clustered intooperational taxonomic units (OTUs) based upon sequence similarity and/orreference-based approaches (e.g., using VAMPS, using MG-RAST, usingQIIME databases), aligned (e.g., using a genome hashing approach, usinga Needleman-Wunsch algorithm, using a Smith-Waterman algorithm), andmapped to reference bacterial genomes (e.g., provided by the NationalCenter for Biotechnology Information), using an alignment algorithm(e.g., Basic Local Alignment Search Tool, FPGA accelerated alignmenttool, BWT-indexing with BWA, BWT-indexing with SOAP, BWT-indexing withBowtie, etc.). Mapping of unidentified sequences can additionally oralternatively include mapping to reference archaeal genomes, viralgenomes and/or eukaryotic genomes. Furthermore, mapping of taxa can beperformed in relation to existing databases, and/or in relation tocustom-generated databases.

Additionally or alternatively, in relation to generating a microbiomefunctional diversity dataset, Block S120 can include extractingcandidate features associated with functional aspects of one or moremicrobiome components of the aggregate set of biological samples S127,as indicated in the microbiome composition dataset. Extracting candidatefunctional features can include identifying functional featuresassociated with one or more of: prokaryotic clusters of orthologousgroups of proteins (COGs); eukaryotic clusters of orthologous groups ofproteins (KOGs); any other suitable type of gene product; an RNAprocessing and modification functional classification; a chromatinstructure and dynamics functional classification; an energy productionand conversion functional classification; a cell cycle control andmitosis functional classification; an amino acid metabolism andtransport functional classification; a nucleotide metabolism andtransport functional classification; a carbohydrate metabolism andtransport functional classification; a coenzyme metabolism functionalclassification; a lipid metabolism functional classification; atranslation functional classification; a transcription functionalclassification; a replication and repair functional classification; acell wall/membrane/envelop biogenesis functional classification; a cellmotility functional classification; a post-translational modification,protein turnover, and chaperone functions functional classification; aninorganic ion transport and metabolism functional classification; asecondary metabolites biosynthesis, transport and catabolism functionalclassification; a signal transduction functional classification; anintracellular trafficking and secretion functional classification; anuclear structure functional classification; a cytoskeleton functionalclassification; a general functional prediction only functionalclassification; and a function unknown functional classification; andany other suitable functional classification.

Additionally or alternatively, extracting candidate functional featuresin Block S127 can include identifying functional features associatedwith one or more of: systems information (e.g., pathway maps forcellular and organismal functions, modules or functional units of genes,hierarchical classifications of biological entities); genomicinformation (e.g., complete genomes, genes and proteins in the completegenomes, ortholog groups of genes in the complete genomes); chemicalinformation (e.g., chemical compounds and glycans, chemical reactions,enzyme nomenclature); health information (e.g., human diseases, approveddrugs, crude drugs and health-related substances); metabolism pathwaymaps; genetic information processing (e.g., transcription, translation,replication and repair, etc.) pathway maps; environmental informationprocessing (e.g., membrane transport, signal transduction, etc.) pathwaymaps; cellular processes (e.g., cell growth, cell death, cell membranefunctions, etc.) pathway maps; organismal systems (e.g., immune system,endocrine system, nervous system, etc.) pathway maps; human diseasepathway maps; drug development pathway maps; and any other suitablepathway map.

In extracting candidate functional features, Block S127 can compriseperforming a search of one or more databases, such as the KyotoEncyclopedia of Genes and Genomes (KEGG) and/or the Clusters ofOrthologous Groups (COGs) database managed by the National Center forBiotechnology Information (NCBI). Searching can be performed based uponresults of generation of the microbiome composition dataset from one ormore of the set of aggregate biological samples. Searching canadditionally or alternatively be performed according to any othersuitable filters. In specific examples, Block S127 can includeextracting candidate functional features, based on the microbiomecomposition dataset, from a KEGG database resource and a COG databaseresource; however, Block S127 can comprise extracting candidatefunctional features in any other suitable manner.

Upon identification of represented groups of microorganisms of themicrobiome associated with a biological sample and/or identification ofcandidate functional aspects (e.g., functions associated with themicrobiome components of the biological samples), generating featuresderived from compositional and/or functional aspects of the microbiomeassociated with the aggregate set of biological samples can beperformed.

In one variation, generating features can include generating featuresderived from multilocus sequence typing (MLST), which can be performedexperimentally at any stage in relation to implementation of the methods100, 200, in order to identify markers useful for characterization insubsequent blocks of the method 100. Additionally or alternatively,generating features can include generating features that describe thepresence or absence of certain taxonomic groups of microorganisms,and/or ratios between exhibited taxonomic groups of microorganisms.Additionally or alternatively, generating features can includegenerating features describing one or more of: quantities of representedtaxonomic groups, networks of represented taxonomic groups, correlationsin representation of different taxonomic groups, interactions betweendifferent taxonomic groups, products produced by different taxonomicgroups, interactions between products produced by different taxonomicgroups, ratios between dead and alive microorganisms (e.g., fordifferent represented taxonomic groups, based upon analysis of RNAs),phylogenetic distance (e.g., in terms of Kantorovich-Rubinsteindistances, Wasserstein distances etc.), any other suitable taxonomicgroup-related feature(s), any other suitable genetic or functionalfeature(s).

Additionally or alternatively, generating features can includegenerating features describing relative abundance of differentmicroorganism groups, for instance, using a sparCC approach, usingGenome Relative Abundance and Average size (GAAS) approach and/or usinga Genome Relative Abundance using Mixture Model theory (GRAMMy) approachthat uses sequence-similarity data to perform a maximum likelihoodestimation of the relative abundance of one or more groups ofmicroorganisms. Additionally or alternatively, generating features caninclude generating statistical measures of taxonomic variation, asderived from abundance metrics. Additionally or alternatively,generating features can include generating features derived fromrelative abundance factors (e.g., in relation to changes in abundance ofa taxon, which affects abundance of other taxa). Additionally oralternatively, generating features can include generation of qualitativefeatures describing presence of one or more taxonomic groups, inisolation and/or in combination. Additionally or alternatively,generating features can include generation of features related togenetic markers (e.g., representative 16S, 18S, and/or ITS sequences)characterizing microorganisms of the microbiome associated with abiological sample. Additionally or alternatively, generating featurescan include generation of features related to functional associations ofspecific genes and/or organisms having the specific genes. Additionallyor alternatively, generating features can include generation of featuresrelated to pathogenicity of a taxon and/or products attributed to ataxon. Block S120 can, however, include generation of any other suitablefeature(s) derived from sequencing and mapping of nucleic acids of abiological sample. For instance, the feature(s) can be combinatory(e.g., involving pairs, triplets), correlative (e.g., related tocorrelations between different features), and/or related to changes infeatures (i.e., temporal changes, changes across sample sites, etc.,spatial changes, etc.). Features can, however, be generated in any othersuitable manner in Block S120.

1.3 First Method: Supplementary Data

Block S130 recites: receiving a supplementary dataset, associated withat least a subset of the population of subjects, wherein thesupplementary dataset is informative of characteristics associated withthe immune microbial dysfunction. Block S130 functions to acquireadditional data associated with one or more subjects of the set ofsubjects, which can be used to train and/or validate thecharacterization processes performed in Block S140. In Block S130, thesupplementary dataset preferably includes survey-derived data, but canadditionally or alternatively include any one or more of: contextualdata derived from sensors, medical data (e.g., current and historicalmedical data), and any other suitable type of data. In variations ofBlock S130 including reception of survey-derived data, thesurvey-derived data preferably provides physiological, demographic, andbehavioral information in association with a subject. Physiologicalinformation can include information related to physiological features(e.g., height, weight, body mass index, body fat percent, body hairlevel, etc.). Demographic information can include information related todemographic features (e.g., gender, age, ethnicity, marital status,number of siblings, socioeconomic status, sexual orientation, etc.).Behavioral information can include information related to one or moreof: health conditions (e.g., health and disease states), livingsituations (e.g., living alone, living with pets, living with asignificant other, living with children, etc.), dietary habits (e.g.,omnivorous, vegetarian, vegan, sugar consumption, acid consumption,etc.), behavioral tendencies (e.g., levels of physical activity, druguse, alcohol use, etc.), different levels of mobility (e.g., related todistance traveled within a given time period), different levels ofsexual activity (e.g., related to numbers of partners and sexualorientation), and any other suitable behavioral information.Survey-derived data can include quantitative data and/or qualitativedata that can be converted to quantitative data (e.g., using scales ofseverity, mapping of qualitative responses to quantified scores, etc.).

In facilitating reception of survey-derived data, Block S130 can includeproviding one or more surveys to a subject of the population ofsubjects, or to an entity associated with a subject of the population ofsubjects. Surveys can be provided in person (e.g., in coordination withsample provision and reception from a subject), electronically (e.g.,during account setup by a subject, at an application executing at anelectronic device of a subject, at a web application accessible throughan internet connection, etc.), and/or in any other suitable manner.

Additionally or alternatively, portions of the supplementary datasetreceived in Block S130 can be derived from sensors associated with thesubject(s) (e.g., sensors of wearable computing devices, sensors ofmobile devices, biometric sensors associated with the user, etc.). Assuch, Block S130 can include receiving one or more of: physicalactivity- or physical action-related data (e.g., accelerometer andgyroscope data from a mobile device or wearable electronic device of asubject), environmental data (e.g., temperature data, elevation data,climate data, light parameter data, etc.), patient nutrition ordiet-related data (e.g., data from food establishment check-ins, datafrom spectrophotometric analysis, etc.), biometric data (e.g., datarecorded through sensors within the patient's mobile computing device,data recorded through a wearable or other peripheral device incommunication with the patient's mobile computing device), location data(e.g., using GPS elements), and any other suitable data. Additionally oralternatively, portions of the supplementary dataset can be derived frommedical record data and/or clinical data of the subject(s). As such,portions of the supplementary dataset can be derived from one or moreelectronic health records (EHRs) of the subject(s).

Additionally or alternatively, the supplementary dataset of Block S130can include any other suitable diagnostic information (e.g., clinicaldiagnosis information), which can be combined with analyses derived fromfeatures to support characterization of subjects in subsequent blocks ofthe method 100. For instance, information derived from a colonoscopy,biopsy, blood test, diagnostic imaging, survey-related information, andany other suitable test can be used to supplement Block S130.

1.4 First Method: Characterizations of the Immune Microbial Dysfunction

Block S140 recites: generating a characterization of the immunemicrobial dysfunction based upon the supplementary dataset and featuresextracted from at least one of the microbiome composition dataset andthe microbiome functional diversity dataset. Block S140 functions toperform a characterization process for identifying features and/orfeature combinations that can be used to characterize subjects or groupswith the immune microbial dysfunction based upon their microbiomecomposition and/or functional features. Additionally or alternatively,the characterization process can be used as a diagnostic tool that cancharacterize a subject (e.g., in terms of behavioral traits, in terms ofmedical conditions, in terms of demographic traits, etc.) based upontheir microbiome composition and/or functional features, in relation toother health condition states, behavioral traits, medical conditions,demographic traits, and/or any other suitable traits. Suchcharacterization can then be used to suggest or provide personalizedtherapies by way of the therapy model of Block S150.

In performing the characterization process, Block S140 can usecomputational methods (e.g., statistical methods, machine learningmethods, artificial intelligence methods, bioinformatics methods, etc.)to characterize a subject as exhibiting features characteristic of agroup of subjects with the immune microbial dysfunction.

In one variation, characterization can be based upon features derivedfrom a statistical analysis (e.g., an analysis of probabilitydistributions) of similarities and/or differences between a first groupof subjects exhibiting a target state (e.g., a health condition state)associated with the immune microbial dysfunction, and a second group ofsubjects not exhibiting the target state (e.g., a “normal” state)associated with the immune microbial dysfunction. In implementing thisvariation, one or more of a Kolmogorov-Smirnov (KS) test, a permutationtest, a Cramér-von Mises test, and any other statistical test (e.g.,t-test, Welch's t-test, z-test, chi-squared test, test associated withdistributions, etc.) can be used. In particular, one or more suchstatistical hypothesis tests can be used to assess a set of featureshaving varying degrees of abundance in a first group of subjectsexhibiting a target state (i.e., an adverse state) associated with theimmune microbial dysfunction and a second group of subjects notexhibiting the target state (i.e., having a normal state) associatedwith the immune microbial dysfunction. In more detail, the set offeatures assessed can be constrained based upon percent abundance and/orany other suitable parameter pertaining to diversity in association withthe first group of subjects and the second group of subjects, in orderto increase or decrease confidence in the characterization. In aspecific implementation of this example, a feature can be derived from ataxon of microorganism and/or presence of a functional feature that isabundant in a certain percentage of subjects of the first group andsubjects of the second group, wherein a relative abundance of the taxonbetween the first group of subjects and the second group of subjects canbe determined from a KS test or a Welch's t-test, with an indication ofsignificance (e.g., in terms of p-value). Thus, an output of Block S140can comprise a normalized relative abundance value (e.g., 25% greaterabundance of a taxon-derived feature and/or a functional feature in sicksubjects vs. healthy subjects) with an indication of significance (e.g.,a p-value of 0.0013). Variations of feature generation can additionallyor alternatively implement or be derived from functional features ormetadata features (e.g., non-bacterial markers).

In performing the characterization process, Block S140 can additionallyor alternatively transform input data from at least one of themicrobiome composition dataset and microbiome functional diversitydataset into feature vectors that can be tested for efficacy inpredicting characterizations of the population of subjects. Data fromthe supplementary dataset can be used to inform characterizations of theimmune microbial dysfunction, wherein the characterization process istrained with a training dataset of candidate features and candidateclassifications to identify features and/or feature combinations thathave high degrees (or low degrees) of predictive power in accuratelypredicting a classification. As such, refinement of the characterizationprocess with the training dataset identifies feature sets (e.g., ofsubject features, of combinations of features) having high correlationwith presence of the immune microbial dysfunction.

In variations, feature vectors effective in predicting classificationsof the characterization process can include features related to one ormore of: microbiome diversity metrics (e.g., in relation to distributionacross taxonomic groups, in relation to distribution across archaeal,bacterial, viral, and/or eukaryotic groups), presence of taxonomicgroups in one's microbiome, representation of specific genetic sequences(e.g., 16S sequences) in one's microbiome, relative abundance oftaxonomic groups in one's microbiome, microbiome resilience metrics(e.g., in response to a perturbation determined from the supplementarydataset), abundance of genes that encode proteins or RNAs with givenfunctions (enzymes, transporters, proteins from the immune system,hormones, interference RNAs, etc.) and any other suitable featuresderived from the microbiome diversity dataset and/or the supplementarydataset. Additionally, combinations of features can be used in a featurevector, wherein features can be grouped and/or weighted in providing acombined feature as part of a feature set. For example, one feature orfeature set can include a weighted composite of the number ofrepresented classes of bacteria in one's microbiome, presence of aspecific genus of bacteria in one's microbiome, representation of aspecific 16S sequence in one's microbiome, and relative abundance of afirst phylum over a second phylum of bacteria. However, the featurevectors can additionally or alternatively be determined in any othersuitable manner.

As shown in FIG. 4, in one such alternative variation of Block S140, thecharacterization process can be generated and trained according to arandom forest predictor (RFP) algorithm that combines bagging (i.e.,bootstrap aggregation) and selection of random sets of features from atraining dataset to construct a set of decision trees, T, associatedwith the random sets of features. In using a random forest algorithm, Ncases from the set of decision trees are sampled at random withreplacement to create a subset of decision trees, and for each node, mprediction features are selected from all of the prediction features forassessment. The prediction feature that provides the best split at thenode (e.g., according to an objective function) is used to perform thesplit (e.g., as a bifurcation at the node, as a trifurcation at thenode). By sampling many times from a large dataset, the strength of thecharacterization process, in identifying features that are strong inpredicting classifications can be increased substantially. In thisvariation, measures to prevent bias (e.g., sampling bias) and/or accountfor an amount of bias can be included during processing to increaserobustness of the model.

1.4.1 Crohn's Disease Characterization

In one implementation, a characterization process of Block S140 basedupon statistical analyses can identify the sets of features that havethe highest correlations with Crohn's disease, for which one or moretherapies would have a positive effect, based upon an algorithm trainedand validated with a validation dataset derived from a subset of thepopulation of subjects. In particular, Crohn's disease in this firstvariation is a gastrointestinal disorder typically diagnosed based onone or more of: colonoscopy-based methods, endoscopy-based methods(e.g., capsule endoscopy), and computed tomography (CT) scans to observemultinucleated giant cells. In the first variation, a set of featuresuseful for diagnostics associated with Crohn's disease includes featuresderived from one or more of the following taxa: Clostridium (genus),Flavonifractor (genus), Prevotella (genus), Clostridiaceae (family),Prevotellaceae (family), Oscillospiraceae (family), Gammaproteobacteria(class), and Proteobacteria (phylum). Additionally or alternatively, theset of features can be derived from one or more of the following taxa:Eggerthella (genus), Akkermansia (genus), Anaerosporobacter (genus),Erysipelothrix (genus), Legionella (genus), Parabacteroides (genus),Odoribacter (genus), Barnesiella (genus), Actinobacillus (genus),Clostridium (genus), Haemophilus (genus), Veillonella (genus),Bacteroides (genus), Megasphaera (genus), Marvinbryantia (genus),Butyricicoccus (genus), Bilophila (genus), Oscillibacter (genus),Butyricimonas (genus), Ruminococcus (genus), Sarcina (genus),Lactobacillus (genus), Streptococcus (genus), Pectobacterium (genus),Coprococcus (genus), Eubacterium (genus), Collinsella (genus),Faecalibacterium (genus), Subdoligranulum (genus), and Cronobacter(genus).

Additionally or alternatively, the set of features associated withCrohn's disease can be derived from one or more of: a COG (D) code(e.g., a cell cycle control, cell division, and chromosome partitioningfunctional feature); a COG (I) code (e.g., a lipid transport andmetabolism functional feature); a COG (J) code (e.g., a translation,ribosomal structure and biogenesis functional feature); a cell growthand death KEGG pathway derived feature; an endocrine system KEGG pathwayderived feature; a folding, sorting, and degradation KEGG pathwayderived feature; a metabolism KEGG pathway derived feature; a metabolismof terpenoids and polyketides KEGG pathway derived feature; areplication and repair KEGG pathway derived feature; a translation KEGGpathway derived feature; an amino acid related enzymes KEGG pathwayderived feature; an aminoacyl-tRNA biosynthesis KEGG pathway derivedfeature; a homologous recombination KEGG pathway derived feature; anucleotide excision repair KEGG pathway derived feature; a PPARsignaling pathway KEGG pathway derived feature; a peptidoglycanbiosynthesis KEGG pathway derived feature; a prion diseases KEGG pathwayderived feature; a ribosome KEGG pathway derived feature; a translationfactors KEGG pathway derived feature; a large subunit ribosomal proteinL20 KEGG derived feature (e.g., K02887 KEGG code associated with RP-L20,MRPL20, and/or rpIT); a Mg²⁺-importing ATPase [EC:2.6.3.2] KEGG derivedfeature (e.g., a K01531 KEGG code associated with mgtA and/or mgtB); apeptidyl-tRNA hydrolase PTH1 family [EC:30.1.1.29] KEGG derived feature(e.g., a K01056 KEGG code associated with PTH1, pth, and/or spoVC); alarge subunit ribosomal protein L13 KEGG derived feature (e.g., a K02871KEGG code associated with RP-L13, MRPL13, and/or rpIM); a type IV pilusassembly protein PilQ KEGG derived feature (e.g., a K02666 KEGG codeassociated with pilQ, where pilus allows attachment of bacterial cellsto the gut wall); a superoxide dismutase, Cu—Zn family [EC:1.15.1.1]KEGG derived feature (e.g., a K04565 KEGG code associated with SOD1); atransposase KEGG derived feature (e.g., a K07487 KEGG code associatedwith transposases that catalyze the replicative transposition oftransposable elements); and a transposase IS30 family KEGG derivedfeature (e.g., a K07482 KEGG code associated with transposases thatcatalyze the replicative transposition of transposable elements). Thus,characterization of the subject comprises characterization of thesubject as someone with Crohn's disease based upon detection of one ormore of the above features, in a manner that is an alternative orsupplemental to typical methods of diagnosis. In variations of thespecific example, the set of features can, however, include any othersuitable features useful for diagnostics.

1.4.2 IBS Characterization

In another implementation, a characterization process of Block S140based upon statistical analyses can identify the sets of features thathave the highest correlations with irritable bowel syndrome (IBS), forwhich one or more therapies would have a positive effect, based upon analgorithm trained and validated with a validation dataset derived from asubset of the population of subjects. In particular, IBS in this firstvariation is a gastrointestinal disorder characterized by chronicabdominal pain, discomfort, bloating, and alteration of bowel habits, astypically assessed by colonscopy and exclusion of other gastrointestinaldisorders (e.g., Celiac disease). In the first variation, a set offeatures useful for diagnostics associated with IBD includes featuresderived from one or more of the following taxa: Flavonifractor (genus),Odoribacter (genus), Blautia (genus), and Finegoldia (genus).Additionally or alternatively, a set of features can be derived from oneor more of the following taxa: Flavonifractor plautii (species),Holdemania (genus), Bacteroides (genus), Bacteroidaceae (family),Alistipes (genus), Rikenellaceae (family), bacterium NLAE-zl-P827(species), Deltaproteobacteria (class), Bilophila (genus),Pasteurellaceae (family), Pasteurellales (order), Gammaproteobacteria(class), Bilophila wadsworthia (species), Clostridiales (order),Clostridia (class), Odoribacter (genus), Clostridium lavalense(species), Odoribacter splanchnicus (species), Coriobacteriaceae(family), Rhodospirillales (order), organismal metagenomes (no rank),Anaerostipes (genus), Actinobacteria (class), Prevotellaceae (family),Rhodospirillaceae (family), bacterium NLAE-zl-H₅₄ (species),Actinobacteridae spp. (no rank), Roseburia sp. 11SE38 (species),Bifidobacteriaceae (family), Bifidobacteriales (order), Bifidobacterium(genus), butyrate-producing bacterium SR1/1 (species), Finegoldia magna(species), Finegoldia (genus), and Peptoniphilus (genus).

Additionally or alternatively, the set of features associated with IBScan be derived from one or more of: pcoC KEGG derived feature (e.g., aK07156 KEGG code); a carboxylate-amine ligase [EC:6.3.-.-] KEGG derivedfeature (e.g., a K06048 KEGG code associated with ybdK); and anisocitrate lyase [EC:40.1.3.1] KEGG derived feature (e.g., a K01637 KEGGcode associated with aceA). Thus, characterization of the subjectcomprises characterization of the subject as someone with IBS based upondetection of one or more of the above features, in a manner that is analternative or supplemental to typical methods of diagnosis. Invariations of the specific example, the set of features can, however,include any other suitable features useful for diagnostics.

1.4.3 IBD Characterization

In another implementation, a characterization process of Block S140based upon statistical analyses can identify the sets of features thathave the highest correlations with inflammatory bowel disease (IBD), forwhich one or more therapies would have a positive effect, based upon analgorithm trained and validated with a validation dataset derived from asubset of the population of subjects. In particular, IBD in this firstvariation is a gastrointestinal disorder characterized by biopsy oncolonoscopy and/or fecal calprotectin. In the first variation, a set offeatures useful for diagnostics associated with IBD includes featuresderived from one or more of the following taxa: Clostridium (genus),Ruminococcus (genus), Clostridiaceae (family), Veillonellaceae (family),Selenomonadales (order), Gammaproteobacteria (class), Negativicutes(class), and Proteobacteria (phylum). Additionally or alternatively, aset of features can be derived from one or more of the following taxa:bacterium NLAE-zl-P562 (species), Actinobacillus porcinus (species),Megasphaera (genus), Actinobacillus (genus), Flavonifractor plautii(species), Pasteurellaceae (family), Pasteurellales (order),Gammaproteobacteria (class), Enterobacteriales (order),Enterobacteriaceae (family), Veillonellaceae (family), Bacteroidesfragilis (species), Lactobacillales (order), Proteobacteria (phylum),Selenomonadales (order), Negativicutes (class), Streptococcaceae(family), Bacilli (class), Cronobacter (genus), Cronobacter sakazakii(species), Streptococcus (genus), Burkholderiales (order),Betaproteobacteria (class), Sutterellaceae (family), Erysipelotrichaceae(family), Erysipelotrichia (class), Erysipelotrichales (order),uncultured Coriobacteriia bacterium (species), Coriobacteriales (order),Coriobacteriaceae (family), Collinsella (genus), Holdemania (genus),Roseburia (genus), Ruminococcaceae (family), Deltaproteobacteria(class), Pseudobutyrivibrio (genus), delta/epsilon subdivisions(subphylum), Desulfovibrionales (order), Christensenellaceae (family),Porphyromonadaceae (family), Acidaminococcaceae (family), Ruminococcus(genus), Marvinbryantia (genus), Chlamydiae/Verrucomicrobia group(superphylum), butyrate-producing bacterium SR1/1 (species),Sphingobacteriales (order), Bacillales (order), Bacillales incertaesedis (no rank), Bacillales Family XI. Incertae Sedis (no rank), andOceanospirillales (order).

Additionally or alternatively, the set of features associated with IBDcan be derived from one or more of: a replication and repair KEGGpathway derived feature; a UDP-N-acetyl-D-glucosamine dehydrogenase[EC:1.1.1.136] KEGG derived feature (e.g., a K13015 KEGG code associatedwith wbpA); a putative glycerol-1-phosphate prenyltransferase[EC:2.5.1.-] KEGG derived feature (e.g., a K07094 KEGG code associatedwith perB); a hypothetical protein KEGG derived feature (e.g., a KomoiKEGG code); a proline dehydrogenase [EC:1.5.-.-] KEGG derived feature(e.g., a K00318 KEGG code associated with PRODH); and a transposase IS30family KEGG derived feature (e.g., a K07482 code associated withtransposases that catalyze the replicative transposition of transposableelements).

Thus, characterization of the subject comprises characterization of thesubject as someone with IBD based upon detection of one or more of theabove features, in a manner that is an alternative or supplemental totypical methods of diagnosis. In variations of the specific example, theset of features can, however, include any other suitable features usefulfor diagnostics.

1.4.4 Ulcerative Colitis Characterization

In another implementation, a characterization process of Block S140based upon statistical analyses can identify the sets of features thathave the highest correlations with ulcerative colitis, for which one ormore therapies would have a positive effect, based upon an algorithmtrained and validated with a validation dataset derived from a subset ofthe population of subjects. In particular, Ulcerative colitis in thisfirst variation is a gastrointestinal disorder typically characterizedby one or more of: a complete blood count, electrolyte studies, renalfunction tests, liver function tests, x-ray imaging, urinalysis,C-reactive protein measurement, and sigmoidoscopy. In the firstvariation, a set of features useful for diagnostics associated withulcerative colitis includes features derived from one or more of thefollowing taxa: Clostridium (genus), Lachnospira (genus), Blautia(genus), Dialister (genus), Ruminococcus (genus), Clostridiaceae(family), Peptostreptococcaceae (family), Veillonellaceae (family),Erysipelotrichaceae (family), Christensenellaceae (family),Erysipelotrichales (order), Gammaproteobacteria (class), andErysipelotrichia (class). Additionally or alternatively, a set offeatures can be derived from one or more of the following taxa:Actinobacillus porcinus (species), Actinobacillus (genus),Pasteurellaceae (family), Pasteurellales (order), Gammaproteobacteria(class), Flavonifractor plautii (species), Flavonifractor (genus),Lactobacillales (order), Lachnospiraceae bacterium 2_1_58FAA (species),Bacilli (class), Veillonellaceae (family), bacterium NLAE-zl-P430(species), Dialister (genus), Parasutterella (genus), Faecalibacterium(genus), Parasutterella excrementihominis (species), Collinsella(genus), Coriobacteriaceae (family), uncultured Coriobacteriia bacterium(species), Coriobacteriales (order), Pseudobutyrivibrio (genus),Bacteroides fragilis (species), Holdemania (genus), Porphyromonadaceae(family), Chlamydiae/Verrucomicrobia group (superphylum), Eggerthellalenta (species), Verrucomicrobia (phylum), Bacteroidales (order),Bacteroidia (class), Bacteroidetes (phylum), Bacteroidetes/Chlorobigroup (superphylum), Verrucomicrobiae (class), Verrucomicrobiales(order), Verrucomicrobiaceae (family), Subdoligranulum (genus), Dorea(genus), Deltaproteobacteria (class), delta/epsilon subdivisions(subphylum), Bacillales incertae sedis (no rank), Desulfovibrionales(order), Ruminococcus (genus), Coprococcus (genus), Eubacteriaceae(family), Eubacterium (genus), Christensenellaceae (family),Acidaminococcaceae (family), Rhodospirillales (order), Marvinbryantia(genus), Rhodospirillaceae (family), Bacillales (order), Alistipesputredinis (species), and Bacillaceae (family).

Additionally or alternatively, the set of features associated withulcerative colitis can be derived from one or more of: a COG (B) code(e.g., chromatin structure and dynamics functional feature); a COG (I)code (e.g., a lipid transport and metabolism functional feature); a cellgrowth and death KEGG pathway derived feature; a metabolism ofterpenoids and polyketides KEGG pathway derived feature; a signaltransduction KEGG pathway derived feature; a translation KEGG pathwayderived feature; a base excision repair KEGG pathway derived feature; acell cycle—Caulobacter KEGG pathway derived feature; a N-Glycanbiosynthesis KEGG pathway derived feature; an Oxidative phosphorylationKEGG pathway derived feature; a putative glycerol-1-phosphateprenyltransferase [EC:2.5.1.-] KEGG derived feature (e.g., a K07094 KEGGcode associated with perB); a 5,10-methylenetetrahydromethanopterinreductase [EC:1.5.98.2] KEGG derived feature (e.g., a K00320 KEGG codeassociated with mer); a glutamate:Na⁺ symporter ESS family KEGG derivedfeature (e.g., a K03312 KEGG code associated with gltS); a putativetransposase KEGG derived feature (e.g., a K07494 KEGG code); adiacylglycerol kinase (ATP) [EC:2.7.1.107] KEGG derived feature (e.g., aK07029 KEGG code associated with dagK); an uncharacterized protein KEGGderived feature (e.g., a K06936 KEGG code); an uncharacterized proteinKEGG derived feature (e.g., a K07161 KEGG code); an uncharacterizedprotein KEGG derived feature (e.g., a K09126 KEGG code); a LPPG:FO2-phospho-L-lactate transferase [EC:2.7.8.28] KEGG derived feature(e.g., a K11212 KEGG code associated with cofD); and aphosphosulfolactate synthase [EC:4.4.1.19] KEGG derived feature (e.g., aK08097 KEGG code associated with comA).

Thus, characterization of the subject comprises characterization of thesubject as someone with ulcerative colitis based upon detection of oneor more of the above features, in a manner that is an alternative orsupplemental to typical methods of diagnosis. In variations of thespecific example, the set of features can, however, include any othersuitable features useful for diagnostics.

1.4.5 Celiac Disease Characterization

In another implementation, a characterization process of Block S140based upon statistical analyses can identify the sets of features thathave the highest correlations with celiac disease, for which one or moretherapies would have a positive effect, based upon an algorithm trainedand validated with a validation dataset derived from a subset of thepopulation of subjects. In particular, celiac disease in this firstvariation is an autoimmune disorder of the small intestine that causesgastrointestinal discomfort, gluten intolerance, fatigue, andnutritional deficiencies. In the first variation, a set of featuresuseful for diagnostics associated with celiac disease includes featuresderived from one or more of the following taxa: Clostridium (genus),Oscillibacter (genus), Sutterella (genus), Clostridiaceae (family),Peptostreptococcaceae (family), Peptococcaceae (family),Oscillospiraceae (family), and Proteobacteria (phylum). Additionally oralternatively, a set of features can be derived from one or more of thefollowing taxa: Parasutterella (genus), Bacteroides uniformis (species),Parasutterella excrementihominis (species), Bacteroides fragilis(species), Acidobacteria (phylum), Actinobacillus (genus),Actinobacillus porcinus (species), Pasteurellaceae (family), andPasteurellales (order).

Additionally or alternatively, the set of features associated withceliac disease can be derived from one or more of: a COG (W) code (e.g.,extracellular structures functional feature); a putative membraneprotein KEGG derived feature (e.g., a K08996 KEGG code associated withyagU); a nitric oxide reductase subunit B [EC:1.7.2.5] KEGG derivedfeature (e.g., a K04561 KEGG code associated with norB); a competenceprotein ComGA KEGG derived feature (e.g., a K02243 KEGG code associatedwith comGA); a competence protein ComGC KEGG derived feature (e.g., aK02245 KEGG code associated with comGC); a DNA replication protein KEGGderived feature (e.g., a K02086 KEGG code associated with dnaD); aseparation ring formation regulator KEGG derived feature (e.g., a K06286KEGG code associated with ezrA); a glyceraldehyde-3-phosphatedehydrogenase (NADP+) [ED:1.2.1.9] KEGG derived feature (e.g., a K00131KEGG code associated with gapN); a leader peptidase (prepilinpeptidase)/N-methyltransferase [EC:3.4.23.43 2.1.1.-] (e.g., a K02236KEGG code associated with comC); a pyruvate oxidase [EC:1.2.3.3] KEGGderived feature (e.g., a K00158 KEGG code associated with poxL); a MFStransporter, SHS family, sialic acid transporter KEGG derived feature(e.g., a K03290 KEGG code associated with nanT); a medium-chainacyl-[acyl-carrier-protein] hydrolase [EC:3.1.2.21] KEGG derived feature(e.g., a K01071 KEGG code associated with MCH); an acyl-CoA hydrolase[EC:3.1.2.20] KEGG derived feature (e.g., a K01073 KEGG code); a glucan1,6-alpha-glucosidase [EC:3.2.1.70] KEGG derived feature (e.g., a K01215KEGG code associated with dexB); a putative membrane protein KEGGderived feature (e.g., a K08987 KEGG code); a hydroxymethylglutaryl-CoAreductase [EC:1.1.1.88] KEGG derived feature (e.g., a K00054 KEGG codeassociated with mvaA); a penicillin-binding protein KEGG derived feature(e.g., a K03693 KEGG code associated with pbp); a competence proteinCoiA KEGG derived feature (e.g., a K06198 KEGG code associated withcoiA); an aminotransferase [EC:2.6.1.-] KEGG derived feature (e.g., aK00841 KEGG code associated with patA); an X-pro dipeptidyl-peptidase[EC:3.4.14.11] KEGG derived feature (e.g., a K01281 KEGG code associatedwith pepXP); a SprT-like protein KEGG derived feature (e.g., a K03095KEGG code associated with sprL); a general stress protein 13 KEGGderived feature (e.g., a K07570 KEGG code associated with GSP13); acompetence protein ComGF KEGG derived feature (e.g., a K02248 KEGG codeassociated with comGF); a penicillin-binding protein 2A [EC:2.4.1.1292.3.2.-] KEGG derived feature (e.g., a K12555 KEGG code associated withpbp2A); a para-aminobenzoate synthetase/4-amino-4-deoxychorismate lyase[EC:2.6.1.85 4.1.3.38] KEGG derived feature (e.g., a K03342 KEGG codeassociated with pabBC); an uncharacterized protein KEGG derived feature(e.g., a K09962 KEGG code); a competence protein ComFA KEGG derivedfeature (e.g., a K02240 KEGG code associated with comFA); and a GMPreductase [EC:1.7.1.7] KEGG derived feature (e.g., a K00364 KEGG codeassociated with guaC).

Thus, characterization of the subject comprises characterization of thesubject as someone with celiac disease based upon detection of one ormore of the above features, in a manner that is an alternative orsupplemental to typical methods of diagnosis. In variations of thespecific example, the set of features can, however, include any othersuitable features useful for diagnostics.

Characterization of the subject(s) can additionally or alternativelyimplement use of a high false positive test and/or a high false negativetest to further analyze sensitivity of the characterization process insupporting analyses generated according to embodiments of the method100.

1.5 First Method: Therapy Models and Provision

As shown in FIG. 1A, in some variations, the first method 100 canfurther include Block S150, which recites: based upon thecharacterization, generating a therapy model configured to correct theimmune microbial dysfunction. Block S150 functions to identify orpredict therapies (e.g., probiotic-based therapies, phage-basedtherapies, small molecule-based therapies, etc.) that can shift asubject's microbiome composition and/or functional features toward adesired equilibrium state in promotion of the subject's health. In BlockS150, the therapies can be selected from therapies including one or moreof: probiotic therapies, phage-based therapies, small molecule-basedtherapies, cognitive/behavioral therapies, physical rehabilitationtherapies, clinical therapies, medication-based therapies, diet-relatedtherapies, and/or any other suitable therapy designed to operate in anyother suitable manner in promoting a user's health. In a specificexample of a bacteriophage-based therapy, one or more populations (e.g.,in terms of colony forming units) of bacteriophages specific to acertain bacteria (or other microorganism) represented in a subject withthe immune microbial dysfunction can be used to down-regulate orotherwise eliminate populations of the certain bacteria. As such,bacteriophage-based therapies can be used to reduce the size(s) of theundesired population(s) of bacteria represented in the subject.Complementarily, bacteriophage-based therapies can be used to increasethe relative abundances of bacterial populations not targeted by thebacteriophage(s) used.

For instance, in relation to the variations of immune microbialdysfunctions in Sections 1.4.1 through 1.4.5 above, therapies (e.g.,probiotic therapies, bacteriophage-based therapies, etc.) can beconfigured to downregulate and/or upregulate microorganism populationsor subpopulations (and/or functions thereof) associated with featurescharacteristic of the immune microbial dysfunction.

In a specific example of probiotic therapies, as shown in FIG. 5,candidate therapies of the therapy model can perform one or more of:blocking pathogen entry into an epithelial cell by providing a physicalbarrier (e.g., by way of colonization resistance), inducing formation ofa mucous barrier by stimulation of goblet cells, enhance integrity ofapical tight junctions between epithelial cells of a subject (e.g., bystimulating up regulation of zona-occludens 1, by preventing tightjunction protein redistribution), producing antimicrobial factors,stimulating production of anti-inflammatory cytokines (e.g., bysignaling of dendritic cells and induction of regulatory T-cells),triggering an immune response, and performing any other suitablefunction that adjusts a subject's microbiome away from a state ofdysbiosis.

In variations, the therapy model is preferably based upon data from alarge population of subjects, which can comprise the population ofsubjects from which the microbiome-related datasets are derived in BlockS110, wherein microbiome composition and/or functional features orstates of health, prior exposure to and post exposure to a variety oftherapeutic measures, are well characterized. Such data can be used totrain and validate the therapy provision model, in identifyingtherapeutic measures that provide desired outcomes for subjects basedupon different microbiome characterizations. In variations, supportvector machines, as a supervised machine learning algorithm, can be usedto generate the therapy provision model. However, any other suitablemachine learning algorithm described above can facilitate generation ofthe therapy provision model.

While some methods of statistical analyses and machine learning aredescribed in relation to performance of the Blocks above, variations ofthe method 100 can additionally or alternatively utilize any othersuitable algorithms in performing the characterization process. Invariations, the algorithm(s) can be characterized by a learning styleincluding any one or more of: supervised learning (e.g., using logisticregression, using back propagation neural networks), unsupervisedlearning (e.g., using an Apriori algorithm, using K-means clustering),semi-supervised learning, reinforcement learning (e.g., using aQ-learning algorithm, using temporal difference learning), and any othersuitable learning style. Furthermore, the algorithm(s) can implement anyone or more of: a regression algorithm (e.g., ordinary least squares,logistic regression, stepwise regression, multivariate adaptiveregression splines, locally estimated scatterplot smoothing, etc.), aninstance-based method (e.g., k-nearest neighbor, learning vectorquantization, self-organizing map, etc.), a regularization method (e.g.,ridge regression, least absolute shrinkage and selection operator,elastic net, etc.), a decision tree learning method (e.g.,classification and regression tree, iterative dichotomiser 3, C4.5,chi-squared automatic interaction detection, decision stump, randomforest, multivariate adaptive regression splines, gradient boostingmachines, etc.), a Bayesian method (e.g., naïve Bayes, averagedone-dependence estimators, Bayesian belief network, etc.), a kernelmethod (e.g., a support vector machine, a radial basis function, alinear discriminate analysis, etc.), a clustering method (e.g., k-meansclustering, expectation maximization, etc.), an associated rule learningalgorithm (e.g., an Apriori algorithm, an Eclat algorithm, etc.), anartificial neural network model (e.g., a Perceptron method, aback-propagation method, a Hopfield network method, a self-organizingmap method, a learning vector quantization method, etc.), a deeplearning algorithm (e.g., a restricted Boltzmann machine, a deep beliefnetwork method, a convolution network method, a stacked auto-encodermethod, etc.), a dimensionality reduction method (e.g., principalcomponent analysis, partial lest squares regression, Sammon mapping,multidimensional scaling, projection pursuit, etc.), an ensemble method(e.g., boosting, boostrapped aggregation, AdaBoost, stackedgeneralization, gradient boosting machine method, random forest method,etc.), and any suitable form of algorithm.

Additionally or alternatively, the therapy model can be derived inrelation to identification of a “normal” or baseline microbiomecomposition and/or functional features, as assessed from subjects of apopulation of subjects who are identified to be in good health. Uponidentification of a subset of subjects of the population of subjects whoare characterized to be in good health (e.g., using features of thecharacterization process), therapies that modulate microbiomecompositions and/or functional features toward those of subjects in goodhealth can be generated in Block S150. Block S150 can thus includeidentification of one or more baseline microbiome compositions and/orfunctional features (e.g., one baseline microbiome for each of a set ofdemographics), and potential therapy formulations and therapy regimensthat can shift microbiomes of subjects who are in a state of dysbiosistoward one of the identified baseline microbiome compositions and/orfunctional features. The therapy model can, however, be generated and/orrefined in any other suitable manner.

Microorganism compositions associated with probiotic therapiesassociated with the therapy model preferably include microorganisms thatare culturable (e.g., able to be expanded to provide a scalable therapy)and non-lethal (e.g., non-lethal in their desired therapeutic dosages).Furthermore, microorganism compositions can comprise a single type ofmicroorganism that has an acute or moderated effect upon a subject'smicrobiome. Additionally or alternatively, microorganism compositionscan comprise balanced combinations of multiple types of microorganismsthat are configured to cooperate with each other in driving a subject'smicrobiome toward a desired state. For instance, a combination ofmultiple types of bacteria in a probiotic therapy can comprise a firstbacteria type that generates products that are used by a second bacteriatype that has a strong effect in positively affecting a subject'smicrobiome. Additionally or alternatively, a combination of multipletypes of bacteria in a probiotic therapy can comprise several bacteriatypes that produce proteins with the same functions that positivelyaffect a subject's microbiome.

In examples of probiotic therapies, probiotic compositions can comprisecomponents of one or more of the identified taxa of microorganisms(e.g., as described in sections 1.4.1 through 1.4.5 above) provided atdosages of 1 million to 10 billion CFUs, as determined from a therapymodel that predicts positive adjustment of a subject's microbiome inresponse to the therapy. Additionally or alternatively, the therapy cancomprise dosages of proteins resulting from functional presence in themicrobiome compositions of subjects without the immune microbialdysfunction. In the examples, a subject can be instructed to ingestcapsules comprising the probiotic formulation according to a regimentailored to one or more of his/her: physiology (e.g., body mass index,weight, height), demographics (e.g., gender, age), severity ofdysbiosis, sensitivity to medications, and any other suitable factor.

Furthermore, probiotic compositions of probiotic-based therapies can benaturally or synthetically derived. For instance, in one application, aprobiotic composition can be naturally derived from fecal matter orother biological matter (e.g., of one or more subjects having a baselinemicrobiome composition and/or functional features, as identified usingthe characterization process and the therapy model). Additionally oralternatively, probiotic compositions can be synthetically derived(e.g., derived using a benchtop method) based upon a baseline microbiomecomposition and/or functional features, as identified using thecharacterization process and the therapy model. In variations,microorganism agents that can be used in probiotic therapies can includeone or more of: yeast (e.g., Saccharomyces boulardii), gram-negativebacteria (e.g., E. coli Nissle), gram-positive bacteria (e.g.,Bifidobacteria bifidum, Bifidobacteria infantis, Lactobacillusrhamnosus, Lactococcus lactis, Lactobacillus plantarum, Lactobacillusacidophilus, Lactobacillus casei, Bacillus polyfermenticus, etc.), andany other suitable type of microorganism agent.

Additionally or alternatively, therapies promoted by the therapy modelof Block S150 can include one or more of: consumables (e.g., food items,beverage items, nutritional supplements), suggested activities (e.g.,exercise regimens, adjustments to alcohol consumption, adjustments tocigarette usage, adjustments to drug usage), topical therapies (e.g.,lotions, ointments, antiseptics, etc.), adjustments to hygienic productusage (e.g., use of shampoo products, use of conditioner products, useof soaps, use of makeup products, etc.), adjustments to diet (e.g.,sugar consumption, fat consumption, salt consumption, acid consumption,etc.), adjustments to sleep behavior, living arrangement adjustments(e.g., adjustments to living with pets, adjustments to living withplants in one's home environment, adjustments to light and temperaturein one's home environment, etc.), nutritional supplements (e.g.,vitamins, minerals, fiber, fatty acids, amino acids, prebiotics,probiotics, etc.), medications, antibiotics, and any other suitabletherapeutic measure.

The first method 100 can, however, include any other suitable blocks orsteps configured to facilitate reception of biological samples fromindividuals, processing of biological samples from individuals,analyzing data derived from biological samples, and generating modelsthat can be used to provide customized diagnostics and/or therapeuticsaccording to specific microbiome compositions of individuals.

2. Second Method: Personalized Diagnostics and Therapeutics

In some embodiments, as noted above, outputs of the first method 100 canbe used to generate diagnostics and/or provide therapeutic measures foran individual based upon an analysis of the individual's microbiome. Assuch, a second method 200 derived from at least one output of the firstmethod 100 can include: receiving a biological sample from a subjectS210; characterizing the subject with a form of an immune microbialdysfunction based upon processing a microbiome dataset derived from thebiological sample S220; and promoting a therapy to the subject with theimmune microbial dysfunction based upon the characterization and thetherapy model S230.

Block S210 recites: receiving a biological sample from the subject,which functions to facilitate generation of a microbiome compositiondataset and/or a microbiome functional diversity dataset for thesubject. As such, processing and analyzing the biological samplepreferably facilitates generation of a microbiome composition datasetand/or a microbiome functional diversity dataset for the subject, whichcan be used to provide inputs that can be used to characterize theindividual in relation to diagnosis of the immune microbial dysfunction,as in Block S220. Receiving a biological sample from the subject ispreferably performed in a manner similar to that of one of theembodiments, variations, and/or examples of sample reception describedin relation to Block S110 above. As such, reception and processing ofthe biological sample in Block S210 can be performed for the subjectusing similar processes as those for receiving and processing biologicalsamples used to generate the characterization(s) and/or the therapyprovision model of the first method 100, in order to provide consistencyof process. However, biological sample reception and processing in BlockS210 can alternatively be performed in any other suitable manner.

Block S220 recites: characterizing the subject with a form of an immunemicrobial dysfunction based upon processing a microbiome dataset derivedfrom the biological sample. Block S220 functions to extract featuresfrom microbiome-derived data of the subject, and use the features topositively or negatively characterize the individual as having a form ofimmune microbial dysfunction. Characterizing the subject in Block S220thus preferably includes identifying features and/or combinations offeatures associated with the microbiome composition and/or functionalfeatures of the microbiome of the subject, and comparing such featureswith features characteristic of subjects with the immune microbialdysfunction. Block S220 can further include generation of and/or outputof a confidence metric associated with the characterization for theindividual. For instance, a confidence metric can be derived from thenumber of features used to generate the classification, relative weightsor rankings of features used to generate the characterization, measuresof bias in the models used in Block S140 above, and/or any othersuitable parameter associated with aspects of the characterizationoperation of Block S140.

In some variations, features extracted from the microbiome dataset canbe supplemented with survey-derived and/or medical history-derivedfeatures from the individual, which can be used to further refine thecharacterization operation(s) of Block S220. However, the microbiomecomposition dataset and/or the microbiome functional diversity datasetof the individual can additionally or alternatively be used in any othersuitable manner to enhance the first method 100 and/or the second method200.

Block S230 recites: promoting a therapy to the subject with the immunemicrobial dysfunction based upon the characterization and the therapymodel. Block S230 functions to recommend or provide a personalizedtherapeutic measure to the subject, in order to shift the microbiomecomposition of the individual toward a desired equilibrium state. Assuch, Block S230 can include correcting the immune microbialdysfunction, or otherwise positively affecting the user's health inrelation to the immune microbial dysfunction. Block S230 can thusinclude promoting one or more therapeutic measures to the subject basedupon their characterization in relation to the immune microbialdysfunction.

In Block S230, providing the therapeutic measure to the subject caninclude recommendation of available therapeutic measures configured tomodulate microbiome composition of the subject toward a desired state.Additionally or alternatively, Block S230 can include provision ofcustomized therapy to the subject according to their characterization(e.g., in relation to a specific type of immune microbial dysfunction).In variations, therapeutic measures can include one or more of:probiotics, bacteriophage-based therapies, consumables, suggestedactivities, topical therapies, adjustments to hygienic product usage,adjustments to diet, adjustments to sleep behavior, living arrangement,adjustments to level of sexual activity, nutritional supplements,medications, antibiotics, and any other suitable therapeutic measure.Therapy provision in Block S230 can include provision of notificationsby way of an electronic device, through an entity associated with theindividual, and/or in any other suitable manner.

In more detail, therapy provision in Block S230 can include provision ofnotifications to the subject regarding recommended therapeutic measuresand/or other courses of action, in relation to health-related goals, asshown in FIG. 6. Notifications can be provided to an individual by wayof an electronic device (e.g., personal computer, mobile device, tablet,head-mounted wearable computing device, wrist-mounted wearable computingdevice, etc.) that executes an application, web interface, and/ormessaging client configured for notification provision. In one example,a web interface of a personal computer or laptop associated with asubject can provide access, by the subject, to a user account of thesubject, wherein the user account includes information regarding thesubject's characterization, detailed characterization of aspects of thesubject's microbiome composition and/or functional features, andnotifications regarding suggested therapeutic measures generated inBlock S150. In another example, an application executing at a personalelectronic device (e.g., smart phone, smart watch, head-mounted smartdevice) can be configured to provide notifications (e.g., at a display,haptically, in an auditory manner, etc.) regarding therapeuticsuggestions generated by the therapy model of Block S150. Notificationscan additionally or alternatively be provided directly through an entityassociated with an subject (e.g., a caretaker, a spouse, a significantother, a healthcare professional, etc.). In some further variations,notifications can additionally or alternatively be provided to an entity(e.g., healthcare professional) associated with the subject, wherein theentity is able to administer the therapeutic measure (e.g., by way ofprescription, by way of conducting a therapeutic session, etc.).Notifications can, however, be provided for therapy administration tothe subject in any other suitable manner.

Furthermore, in an extension of Block S230, monitoring of the subjectduring the course of a therapeutic regimen (e.g., by receiving andanalyzing biological samples from the subject throughout therapy, byreceiving survey-derived data from the subject throughout therapy) canbe used to generate a therapy-effectiveness model for each recommendedtherapeutic measure provided according to the model generated in BlockS150.

The methods 100, 200 and/or system of the embodiments can be embodiedand/or implemented at least in part as a machine configured to receive acomputer-readable medium storing computer-readable instructions. Theinstructions can be executed by computer-executable componentsintegrated with the application, applet, host, server, network, website,communication service, communication interface,hardware/firmware/software elements of a patient computer or mobiledevice, or any suitable combination thereof. Other systems and methodsof the embodiments can be embodied and/or implemented at least in partas a machine configured to receive a computer-readable medium storingcomputer-readable instructions. The instructions can be executed bycomputer-executable components integrated with apparatuses and networksof the type described above. The computer-readable medium can be storedon any suitable computer readable media such as RAMs, ROMs, flashmemory, EEPROMs, optical devices (CD or DVD), hard drives, floppydrives, or any suitable device. The computer-executable component can bea processor, though any suitable dedicated hardware device can(alternatively or additionally) execute the instructions.

The FIGURES illustrate the architecture, functionality and operation ofpossible implementations of systems, methods and computer programproducts according to preferred embodiments, example configurations, andvariations thereof. In this regard, each block in the flowchart or blockdiagrams may represent a module, segment, step, or portion of code,which comprises one or more executable instructions for implementing thespecified logical function(s). It should also be noted that, in somealternative implementations, the functions noted in the block can occurout of the order noted in the FIGURES. For example, two blocks shown insuccession may, in fact, be executed substantially concurrently, or theblocks may sometimes be executed in the reverse order, depending uponthe functionality involved. It will also be noted that each block of theblock diagrams and/or flowchart illustration, and combinations of blocksin the block diagrams and/or flowchart illustration, can be implementedby special purpose hardware-based systems that perform the specifiedfunctions or acts, or combinations of special purpose hardware andcomputer instructions.

As a person skilled in the art will recognize from the previous detaileddescription and from the figures and claims, modifications and changescan be made to the embodiments of the invention without departing fromthe scope of this invention as defined in the following claims.

We claim:
 1. A method for characterizing a set of gastrointestinalconditions comprising a Crohn's disease condition, an irritable bowelsyndrome (IBS) condition, an inflammatory bowel disease (IBD) condition,and an ulcerative colitis condition, the method comprising: receiving aset of samples from a population of subjects comprising at least onesubject associated with at least one of the set of gastrointestinalconditions; for each sample of the set of samples: determining amicroorganism nucleic acid sequence, comprising: selecting a primer fora nucleic acid sequence; fragmenting nucleic acid material based on thesample; and amplifying the fragmented nucleic acid material based on theprimer; and determining an alignment of the microorganism nucleic acidsequence to a reference nucleic acid sequence; generating a microbiomecomposition diversity dataset and a microbiome functional diversitydataset for the population of subjects based upon the alignments;collecting a supplementary dataset, associated with at least a subset ofthe population of subjects, wherein the supplementary dataset isinformative of a characteristic associated with the at least one of theset of gastrointestinal conditions; generating a set ofcharacterizations for the set of gastrointestinal conditions based uponthe supplementary dataset and at least one of the microbiome compositiondiversity dataset and the microbiome functional diversity dataset; basedupon the set of characterizations, generating a therapy model thatdetermines a therapy for correcting the at least one of the set ofgastrointestinal conditions; and at an output device associated with asubject, providing the therapy to the subject based upon the therapymodel, wherein the therapy modulates microbiome composition of thesubject towards an equilibrium state.
 2. The method of claim 1, furthercomprising: providing a set of sampling kits to the population ofsubjects, each sampling kit of the set of sampling kits comprising asample container configured to receive the sample from a collectionsite, wherein determining the microorganism nucleic acid sequencecomprises determining the microorganism nucleic acid sequence with abridge amplification substrate of a next generation sequencing platformof a sample processing system, and wherein generating the microbiomecomposition diversity dataset and the microbiome functional diversitydataset comprises generating the microbiome composition diversitydataset and the microbiome functional diversity dataset at computingdevices operable to communicate with the next generation sequencingplatform.
 3. The method of claim 2, wherein determining themicroorganism nucleic acid sequence comprises performing, at a librarypreparation subsystem of the sample processing system, multiplexamplification with the fragmented nucleic acid material based on theprimer.
 4. The method of claim 1, wherein selecting the primer comprisesselecting the primer for the nucleic acid sequence associated with a 16SRNA sequence.
 5. The method of claim 4, wherein generating the set ofcharacterizations comprises generating the set of characterizationsbased on a set of features associated with the 16S RNA sequence andcomprising a relative abundance of different taxonomic groupsrepresented in the microbiome composition diversity dataset.
 6. Themethod of claim 5, wherein the population of subjects comprises a firstsubset exhibiting the at least one of the set of gastrointestinalconditions and a second subset not exhibiting the at least one of theset of gastrointestinal conditions, and wherein the set of featurescomprises a comparison between the first subset and the second subsetfor the relative abundance of different taxonomic groups.
 7. The methodof claim 1, further comprising determining, for the subject, a set ofrisks for the set of gastrointestinal conditions based on the set ofcharacterizations and at least one of a subject microbiome compositiondiversity dataset and a subject microbiome functional diversity datasetassociated with a subject sample from the subject, wherein the therapyis operable to reduce the set of risks.
 8. The method of claim 1,wherein generating the set of characterizations for the set ofgastrointestinal conditions comprises generating the set ofcharacterizations based on a set of microbiome composition featuresextracted from the microbiome composition diversity dataset, wherein theset of microbiome composition features are associated with a set of taxacomprising at least one of: Alistipes (genus), Barnesiella (genus),Bifidobacterium (genus), Clostridium (genus), Lactobacillus (genus),Odoribacter (genus), Prevotella (genus), Flavonifractor (genus),Roseburia (genus), Ruminococcus (genus), Veillonella (genus),Akkermansia (genus), Bacteroides (genus), Pseudobutyrivibrio (genus),Collinsella (genus), Coprococcus (genus), Desulfovibrionales (order),Dialister (genus), Faecalibacterium (genus), and Streptococcus (genus).9. The method of claim 8, wherein the set of gastrointestinal conditionscomprises a gastrointestinal symptom comprising at least one ofabdominal pain, bloating, gastrointestinal discomfort, and alteration ofbowel habits, wherein selecting the primer comprises selecting theprimer for the nucleic acid sequence associated with thegastrointestinal symptom, and wherein generating the set ofcharacterizations comprises generating a characterization of thegastrointestinal symptom.
 10. The method of claim 8, wherein the set ofmicrobiome composition features are associated with the set of taxafurther comprising at least one of: Clostridiaceae (family),Prevotellaceae (family), Oscillospiraceae (family), Gammaproteobacteria(class), Proteobacteria (phylum), Eggerthella (genus), Anaerosporobacter(genus), Erysipelothrix (genus), Legionella (genus), Parabacteroides(genus), Barnesiella (genus), Actinobacillus (genus), Haemophilus(genus), Megasphaera (genus), Marvinbryantia (genus), Butyricicoccus(genus), Bilophila (genus), Oscillibacter (genus), Butyricimonas(genus), Sarcina (genus), Pectobacterium (genus), Eubacterium (genus),Subdoligranulum (genus), Cronobacter (genus), Lachnospira (genus),Blautia (genus, Peptostreptococcaceae (family), Veillonellaceae(family), Erysipelotrichaceae (family), Christensenellaceae (family),Erysipelotrichales (order), Erysipelotrichia (class), Actinobacillusporcinus (species), Pasteurellaceae (family), Pasteurellales (order),Flavonifractor plautii (species), Lactobacillales (order),Lachnospiraceae bacterium 2_1_58FAA (species), Bacilli (class),bacterium NLAE-zl-P430 (species), Parasutterella (genus), Parasutterellaexcrementihominis (species), Coriobacteriaceae (family), unculturedCoriobacteriia bacterium (species), Coriobacteriales (order),Bacteroides fragilis (species), Holdemania (genus), Porphyromonadaceae(family), Chlamydiae/Verrucomicrobia group (superphylum), Eggerthellalenta (species), Verrucomicrobia (phylum), Bacteroidales (order),Bacteroidia (class), Bacteroidetes (phylum), Bacteroidetes/Chlorobigroup (superphylum), Verrucomicrobiae (class), Verrucomicrobiales(order), Verrucomicrobiaceae (family), Dorea (genus),Deltaproteobacteria (class), delta/epsilon subdivisions (subphylum),Bacillales incertae sedis (no rank), Desulfovibrionales (order),Eubacteriaceae (family), Acidaminococcaceae (family), Rhodospirillales(order), Rhodospirillaceae (family), Bacillales (order), Alistipesputredinis (species), and Bacillaceae (family), Selenomonadales (order),Gammaproteobacteria (class), Negativicutes (class), bacteriumNLAE-zl-P562 (species), Enterobacteriales (order), Enterobacteriaceae(family), Streptococcaceae (family), Cronobacter sakazakii (species),Streptococcus (genus), Burkholderiales (order), Betaproteobacteria(class), Sutterellaceae (family), Ruminococcaceae (family),butyrate-producing bacterium SR1/1 (species), Sphingobacteriales(order), Bacillales Family XI. Incertae Sedis, Oceanospirillales(order), Finegoldia (genus), Rikenellaceae (family), Bilophilawadsworthia (species), Clostridiales (order), Clostridia (class),Clostridium lavalense (species), Odoribacter splanchnicus (species),organismal metagenomes (no rank), Anaerostipes (genus), Actinobacteria(class), bacterium NLAE-zl-H54 (species), Actinobacteridae spp. (norank), Roseburia sp. 11SE38 (species), Bifidobacteriaceae (family),Bifidobacteriales (order), Finegoldia magna (species), Finegoldia(genus), and Peptoniphilus (genus).
 11. The method of claim 8, whereingenerating the set of characterizations for the set of gastrointestinalconditions comprises generating the set of characterizations based onthe set of microbiome composition features and a set of microbiomefunctional diversity features extracted from the microbiome functionaldiversity dataset, wherein the set of microbiome functional diversityfeatures comprise at least one of: a clusters of orthologous groups ofproteins (COG) feature set and a Kyoto Encyclopedia of Genes and Genomes(KEGG) feature set.
 12. The method of claim 11, wherein the set ofmicrobiome functional diversity features comprises at least one of: aCOG (D) code derived feature, a COG (I) code derived feature, a COG (J)code derived feature, a cell growth and death KEGG pathway derivedfeature, an endocrine system KEGG pathway derived feature, a folding,sorting, and degradation KEGG pathway derived feature, a metabolism KEGGpathway derived feature, a metabolism of terpenoids and polyketides KEGGpathway derived feature, a replication and repair KEGG pathway derivedfeature, a translation KEGG pathway derived feature, an amino acidrelated enzymes KEGG pathway derived feature, an aminoacyl-tRNAbiosynthesis KEGG pathway derived feature, a homologous recombinationKEGG pathway derived feature, a nucleotide excision repair KEGG pathwayderived feature, a PPAR signaling pathway KEGG pathway derived feature,a peptidoglycan biosynthesis KEGG pathway derived feature, a priondiseases KEGG pathway derived feature, a ribosome KEGG pathway derivedfeature, a translation factors KEGG pathway derived feature, a largesubunit ribosomal protein L20 KEGG derived feature, a Mg²⁺-importingATPase KEGG derived feature, a peptidyl-tRNA hydrolase PTH1 family KEGGderived feature, a large subunit ribosomal protein L13 KEGG derivedfeature, a type IV pilus assembly protein PilQ KEGG derived feature, asuperoxide dismutase, Cu—Zn family KEGG derived feature, a transposaseKEGG derived feature, a transposase IS30 family KEGG derived feature, aCOG (B) code derived feature, a signal transduction KEGG pathway derivedfeature, a base excision repair KEGG pathway derived feature, a cellcycle—Caulobacter KEGG pathway derived feature, a N-Glycan biosynthesisKEGG pathway derived feature, an Oxidative phosphorylation KEGG pathwayderived feature, a putative glycerol-1-phosphate prenyltransferase KEGGderived feature, a 5,10-methylenetetrahydromethanopterin reductase KEGGderived feature, a glutamate:Na⁺ symporter ESS family KEGG derivedfeature, a putative transposase KEGG derived feature, a diacylglycerolkinase KEGG derived feature, an uncharacterized protein KEGG derivedfeature, a LPPG:FO 2-phospho-L-lactate transferase KEGG derived feature,a phosphosulfolactate synthase KEGG derived feature, aUDP-N-acetyl-D-glucosamine dehydrogenase KEGG derived feature, ahypothetical protein KEGG derived feature, a proline dehydrogenase KEGGderived feature, pcoC KEGG derived feature, a carboxylate-amine ligaseKEGG derived feature, and an isocitrate lyase KEGG derived feature. 13.A method for characterizing at least one of a set of gastrointestinalconditions for a subject, the method comprising: for each sample of aset of samples associated with a set of subjects comprising at least onesubject associated with the at least one of the set of gastrointestinalconditions: determining a microorganism nucleic acid sequence,comprising: selecting a primer for a nucleic acid sequence; andamplifying nucleic acid material from the sample based on the primer;and determining an alignment of the microorganism nucleic acid sequenceto a reference nucleic acid; generating at least one of a microbiomecomposition diversity dataset and a microbiome functional diversitydataset based on the alignments; receiving a supplementary datasetassociated with the at least one of the set of gastrointestinalconditions and at least a subset of the set of subjects; generating acharacterization for the at least one of the set of gastrointestinalconditions based upon the supplementary dataset and the at least one ofthe microbiome composition diversity dataset and the microbiomefunctional diversity dataset; based upon the characterization,determining a therapy for the subject; and providing the therapy to thesubject, wherein the therapy is operable to modulate microbiomecomposition of the subject in association with the at least one of theset of gastrointestinal conditions.
 14. The method of claim 13, whereinselecting the primer comprises selecting the primer complementary to thenucleic acid sequence associated with a 16S RNA sequence, and whereingenerating the characterization comprises determining a relativeabundance of different taxonomic groups represented in the microbiomecomposition based on a feature derived from the 16S RNA sequence. 15.The method of claim 13, further comprising: collecting a behavioralsupplementary dataset for the subject; and determining a cause for theat least one of the set of gastrointestinal conditions for the subjectbased on the behavioral supplementary dataset and a subject sample fromthe subject, wherein providing the therapy comprises providing thetherapy based on the behavioral supplementary dataset.
 16. The method ofclaim 13, wherein the at least one of the set of gastrointestinalconditions comprises a Crohn's disease condition, wherein generating thecharacterization comprises generating the characterization based on aset of microbiome composition features extracted from the microbiomecomposition diversity dataset and on a set of microbiome functionaldiversity features extracted from the microbiome functional diversitydataset, wherein the set of microbiome composition features areassociated with a first set of taxa comprising at least one of:Clostridium (genus), Flavonifractor (genus), Prevotella (genus),Clostridiaceae (family), Prevotellaceae (family), Oscillospiraceae(family), Gammaproteobacteria (class), and Proteobacteria (phylum), andwherein the set of microbiome functional diversity features comprises afirst set of functional features comprising at least one of: a clustersof orthologous groups of proteins (COG) (D) code derived feature, a COG(I) code derived feature, a COG (J) code derived feature, a cell growthand death Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway derivedfeature, an endocrine system KEGG pathway derived feature, a folding,sorting, and degradation KEGG pathway derived feature, a metabolism KEGGpathway derived feature, a metabolism of terpenoids and polyketides KEGGpathway derived feature, a replication and repair KEGG pathway derivedfeature, a translation KEGG pathway derived feature, an amino acidrelated enzymes KEGG pathway derived feature, an aminoacyl-tRNAbiosynthesis KEGG pathway derived feature, a homologous recombinationKEGG pathway derived feature, a nucleotide excision repair KEGG pathwayderived feature, a PPAR signaling pathway KEGG pathway derived feature,a peptidoglycan biosynthesis KEGG pathway derived feature, a priondiseases KEGG pathway derived feature, a ribosome KEGG pathway derivedfeature, a translation factors KEGG pathway derived feature, a largesubunit ribosomal protein L20 KEGG derived feature, a Mg²⁺-importingATPase KEGG derived feature, a peptidyl-tRNA hydrolase PTH1 family KEGGderived feature, a large subunit ribosomal protein L13 KEGG derivedfeature, a type IV pilus assembly protein PilQ KEGG derived feature, asuperoxide dismutase, Cu—Zn family KEGG derived feature, a transposaseKEGG derived feature, and a transposase IS30 family KEGG derivedfeature.
 17. The method of claim 16, wherein the at least one of the setof gastrointestinal conditions comprises an irritable bowel syndrome(IBS) condition, wherein the set of microbiome composition features areassociated with a second set of taxa comprising at least one of:Flavonifractor (genus), Odoribacter (genus), Blautia (genus), andFinegoldia (genus), and wherein the set of microbiome functionaldiversity features comprises a second set of functional featurescomprising at least one of: pcoC KEGG derived feature, acarboxylate-amine ligase KEGG derived feature, and an isocitrate lyaseKEGG derived feature.
 18. The method of claim 17, wherein the at leastone of the set of gastrointestinal conditions comprises an inflammatorybowel disease (IBD) condition, wherein the set of microbiome compositionfeatures are associated with a third set of taxa comprising at least oneof: Clostridium (genus), Ruminococcus (genus), Clostridiaceae (family),Veillonellaceae (family), Selenomonadales (order), Gammaproteobacteria(class), Negativicutes (class), and Proteobacteria (phylum), and whereinthe set of microbiome functional diversity features comprises a thirdset of functional features comprising at least one of: aUDP-N-acetyl-D-glucosamine dehydrogenase KEGG derived feature, aputative glycerol-1-phosphate prenyltransferase KEGG derived feature, ahypothetical protein KEGG derived feature, a proline dehydrogenase KEGGderived feature, and the transposase IS30 family KEGG derived feature.19. The method of claim 18, wherein the at least one of the set ofgastrointestinal conditions comprises an ulcerative colitis condition,wherein the set of microbiome composition features are associated with afourth set of taxa comprising at least one of: Clostridium (genus),Lachnospira (genus), Blautia (genus), Dialister (genus), Ruminococcus(genus), Clostridiaceae (family), Peptostreptococcaceae (family),Veillonellaceae (family), Erysipelotrichaceae (family),Christensenellaceae (family), Erysipelotrichales (order),Gammaproteobacteria (class), and Erysipelotrichia (class), and whereinthe set of microbiome functional diversity features comprises a fourthset of functional features comprising at least one of: a COG (B) codederived feature, the COG (I) code derived feature, a cell growth anddeath KEGG pathway derived feature, the metabolism of terpenoids andpolyketides KEGG pathway derived feature, a signal transduction KEGGpathway derived feature, the translation KEGG pathway derived feature, abase excision repair KEGG pathway derived feature, a cellcycle—Caulobacter KEGG pathway derived feature, a N-Glycan biosynthesisKEGG pathway derived feature, an Oxidative phosphorylation KEGG pathwayderived feature, the putative glycerol-1-phosphate prenyltransferaseKEGG derived feature, a 5,10-methylenetetrahydromethanopterin reductaseKEGG derived feature, a glutamate:Na⁺ symporter ESS family KEGG derivedfeature, a putative transposase KEGG derived feature, a diacylglycerolkinase KEGG derived feature, an uncharacterized protein KEGG derivedfeature, a LPPG:FO 2-phospho-L-lactate transferase KEGG derived feature,and a phosphosulfolactate synthase KEGG derived feature.
 20. The methodof claim 19, wherein providing the therapy comprises providing aconsumable operable to selectively modulate a population size of adesired taxon associated with at least one of the first, the second, thethird, and the fourth set of taxa, and at least one of the first, thesecond, the third, and the fourth set of functional features.